This fits with the neurodevelopmental insult and imbalance in excitatory and inhibitory transmission hypothesis for both autism and schizophrenia.20, Specific deletions associated with schizophrenia include 22q11.2, 1q21.1, and 15q13.3, which have been found to be associated with autism, attention-deficit disorder, and mental retardation.20 In individuals with velocardiofacial syndrome (chromosome 22q11), rates of ASD and psychosis are higher.21 Similarly, 16p11.2 microdeletions or microduplications have been reported in 1% of cases of autism and in 2% of the NIMH COS cohort.22-24 These copy number variants confer a risk for a range of neurodevelopmental phenotypes that include autism and schizophrenia.20 Although there have not been systemic comparisons of genome-wide association studies for autism and schizophrenia, some functional links have been reported at voltage-gated calcium channel genes, which are integral to presynaptic function and plasticity, across phenotypes.20, Both autism and schizophrenia have accelerated trajectories of brain development around the age of symptom onset: those with autism have an acceleration or brain overgrowth during the first 3 years of life, and those with COS have an acceleration of brain development (pruning) during adolescence.7, Cheung and colleagues25 attempted to quantify brain structural similarities and differences in ASD and schizophrenia using a quantified anatomical likelihood estimation approach to synthesize existing brain imaging datasets. Further complicating diagnostic precision, both disorders often co-occur with other conditions—ASD frequently co-occurs with disorders such as ADHD, tic disorders, developmental coordination disorder, intellectual disability, depression, and anxiety (29), and SZ frequently co-occurs with panic disorder, posttraumatic stress disorder, obsessive compulsive disorder, depression, anxiety, and substance abuse disorders (30). 1995;245:70-79. J Autism Dev Disord (2009) 39(5):693–705. These symptoms, present since early childhood, predated his symptoms of psychosis and continue to require the support of autism-specific services. We first examined the utility of the ADOS-2 in classifying participants with ASD, SZ, or TD by comparing ADOS-2 cut-off scores with clinical diagnostic consensus by expert licensed clinical psychologists based on information obtained from the ADOS-2, SCID-R, developmental history, collateral information, and the expert opinion of licensed clinical psychologists. For the present study, we recruited community samples of adults with ASD, SZ, and typical development (TD) and administered gold-standard diagnostic interviews for both ASD and SZ. 1991;148:1705-1707. George also had unusual behaviors and mood-regulation difficulties. A final limitation is that, paralleling clinical activity in ASD and SZ, this study was not supported by neuroimaging, electroencephalography, or genetic data. Next, we tested whether the positive/negative framework for categorizing ASD symptomology put forth by Foss-Feig, McPartland (34) could shed light on shared and distinct clinical characteristics in ASD and SZ and improve diagnostic discrimination. What new information does this article add? Higher scores on the PANSS represent greater severity of SZ traits. Seventeen out of 39 participants (43.59%) with a SZ diagnosis met the ADOS-2 criteria for autism or autism-spectrum despite not meeting the DSM-5 criteria for ASD by consensus diagnosis (Table 2). One-hundred and thirty-two individuals participated in this study. Dual Diagnosis of Schizophrenia and Substance Use Disorder Genome-wide studies aid investigation. 5. Such measurement issues are not unique to the ADOS-2; in unpublished work from our group, we have found that both direct assessment and caregiver/self-report measures of ASD symptoms suffer from similar lack of specificity. WB Saunders. Asarnow RF, Brown W, Strandburg R. Children with a schizophrenic disorder: neurobehavioral studies. This was the first time that negative and positive ASD symptoms have been split apart within a clinical measure of ASD symptoms and doing so seems to improve sensitivity and specificity. PLoS One. By 1980, the “Diagnostic and Statistical Manual of Mental Disorders” (DSM) listed autism and schizophrenia as distinct diagnoses. Opler L, Kay S, Lindenmayer J, Fiszbein A. Hum Mol Genet. doi: 10.1093/schbul/11.3.364, 49. The ADOS-2 was administered by trained, research-reliable clinicians and consists of semistructured activities and conversations meant to sample a participant’s real-world social behavior and core autistic characteristics related to language and communication, reciprocal social interaction, imagination and creativity, stereotyped behaviors and restricted interests, and other atypical behaviors. doi: 10.1177/0952695113484320. Adopting this framework from the SZ literature offers a new way of conceptualizing ASD symptomology that could better capture heterogeneity and allow for a dimensional approach to studying and treating shared and distinct symptomology across overlapping diagnostic categories. Los Angeles, CA: Western Psychological Corporation (2012). Walsh T, McClellan JM, McCarthy SE, et al. Mandy W. The Research Domain Criteria: A new dawn for neurodiversity research? Autistic disorders and schizophrenia: related or remote? Buitelaar JK, van der Gaag RJ. We hypothesized that the ADOS-2 would have good sensitivity in ASD but poor specificity in SZ. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. AA and VS were involved with conceptualization of the study, participant recruitment and assessment. However, the rating on the ADOS-2 item as currently written is identical. Adult psychiatrists may benefit from additional training in the diagnosis of ASD in adults, whereas child psychiatrists may benefit from increased comfort with identifying primary psychotic symptoms in autistic youth. Participants were matched on mean age but there were statistically significant group differences in IQ (see Table 1), F(2,129) = 13.661, p < .001, such that the SZ group had significantly lower IQ than the ASD group (p = .006) and the TD group (p < .001). Therefore, we ran Brown––Forsythe tests to examine equality of means and Games–Howell post hoc comparisons, which are more robust to homogeneity of variance violations. The differential diagnosis between these disorders and the comorbid diagnoses of the two conditions is often a bit of a quagmire for clinicians. J Dev Behav Pediatr. 20. Psychiatric comorbidities and schizophrenia. doi: 10.1016/S0193-953X(18)30171-0, 28. The positive and negative syndrome scale (PANSS) for schizophrenia. 14. Neuropsychological function and dysfunction in schizophrenia and psychotic affective disorders. Carroll LS, Owen MJ. On the other hand, positive symptoms related to odd or excessive emotional gestures, echolalia, stereotyped speech patterns, unusual mannerisms, or circumscribed interests may be most indicative of an ASD diagnosis. 19. Am J Psychiatry. A professor is studying the differences between the social impairments found in autism and schizophrenia to help develop better treatments for people with both disorders. 1995;34:1273-1283. A pilot study of D-cycloserine in subjects with autistic disorder. 2004;161:2115-2117. ASD, Autism Spectrum Disorder; SZ. 3rd edition. II. Sprong M, Becker HE, Schothorst PF, et al. All analyses on diagnostic accuracy are based on the ADOS-2 algorithm cut-off scores and the subset of items that comprise this algorithm. Indeed, despite similar deficits in facial emotion recognition in ASD and SZ, there are markedly different patterns of EEG- and fMRI-measured neurological dysfunction associated with these deficits (46, 47). Expert Opin Pharmacother. His thoughts are more linear, he rarely talks about “she,” and he is much more able to engage in his schoolwork. Appropriate identification of comorbid conditions can enhance intervention efforts (eg, autism-related services for those with comorbid ASD and/or use of antipsychotics in patients who have comorbid ASD and a psychotic disorder). Comparison of social cognitive functioning in schizophrenia and high functioning autism: more convergence than divergence. In our analysis with the ADOS-2, there were 11 items where one or more of the codes could not be categorized as either positive or negative. However, there were no statistically significant differences between the ASD and SZ groups for negative ASD symptoms (p = .087). USA: American Psychiatric Publishing (1980). Not surprisingly, these disorders frequently co-occur. Negative symptoms refer to the absence or reduction of characteristics or behaviors that are present in typical development, such as flat facial affect, or paucity of communicative gestures. doi: 10.1016/j.schres.2013.05.013, 25. Table 2 displays the sensitivity, specificity, PPV, and NPV of the ADOS-2, derived by examining the proportions of participants from each subsample whose scores on the ADOS-2 accurately corresponded with the DSM-5 diagnoses determined by all the available information and clinical judgment. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. watman / Adobe Stock. doi: 10.1177/0957154X19832776. Schizophrenia; TD, Typical Development. The TD group also had higher IQ than the ASD group (p = .018). The ADOS reliably discriminated ASD and TD adults, but there was a high rate of “false positives” in SZ patients who did not meet the DSM-5 criteria for ASD. J Clin Psychiatry. Psychiatry 11:548. doi: 10.3389/fpsyt.2020.00548. For both analyses, tests for homogeneity of variances were violated. Some mildly affected individuals may exhibit only slight delays in language and greater challenges with social interactions. 9. Childhood-onset schizophrenia (COS), considered a rare and severe form of schizophrenia, frequently presents with premorbid developmental abnormalities. Lam KS, Bodfish JW, Piven J. Table 3 shows intercorrelations between ADOS-Positive, ADOS-Negative, PANSS-Positive, and PANSS-Negative across the entire sample. It has also discovered that people in … Eur Arch Psychiatry Clin Neurosci. Bastiaansen JA, Meffert H, Hein S, Huizinga P, Ketelaars C, Pijnenborg M, et al. And, perhaps, some schizophrenic kids … Limitations of this study include the small sample size and unequal sex and IQ among the different diagnosis groups. Psychiatr Clinics North Am (1993) 16(2):217–44. • We like to “keep it simple”, but this may not be possible • Change in diagnoses with aging. Also, the disorders are treated differently.2,3 Schizophrenia is thought to develop at a chance rate in individuals with autism. Asperger disorder in adults. doi: 10.1007/s10803-015-2539-x. In contrast, positive items did a good job discriminating the ASD and SZ samples, AUC = .81, p < .001. The patients/participants provided their written informed consent to participate in this study. Therefore, we ran Brown–Forsythe tests to examine quality of means and Games–Howell post hoc comparisons, which are more robust to homogeneity of variances violations. 18. Martínez A, Tobe R, Dias EC, Ardekani BA, Veenstra-VanderWeele J, Patel G, et al. J Autism Dev Disord (2001) 31(1):19–28. New research at Swinburne has revealed a significant overlap in the traits associated with autism and schizophrenia. 2008;69(suppl 4):15-20. ‘Dementia praecocissima’: the Sante De Sanctis model of mental disorder in child psychiatry in the 20th century. I. 20. Rutter M. Childhood schizophrenia reconsidered. At the Yale Child Study Center, a subgroup of children with ASD was labeled as having multiplex developmental disorder.13,14 Researchers in the Netherlands used the term “multiple complex developmental disorders” (MCDD) to describe children who met criteria for ASD and also exhibited affect dysregulation and disordered thinking.15-18 Of significant interest are follow-up studies, which showed that psychosis developed by adulthood in 64% of children with MCDD.16. 39. Our program is frequently asked to rule out ASD, schizotypal personality disorder and/or schizophreniform disorder, and first-episode schizophrenia in youths and young adults. All rights reserved. To test our prediction that the ADOS would be more effective at discriminating the ASD and TD groups versus the ASD and SZ groups, we constrained the samples to just the ASD and TD groups in one analysis and just the ASD and SZ groups in a second analysis. The distinction between the two disorders remained unclear for nearly 30 years, until DSM-II included children with autism under the diagnostic umbrella of schizophrenia, childhood type. doi: 10.1097/CHI.0b013e31818b1c63, 11. These deficits were found in 28% to 55% of children with ASD, and these observations have been replicated in multiple studies.6-8. Dual Diagnosis. The ROC curve for the ASD + SZ samples was also statistically significant, indicating that the ADOS-2 is able to correctly classify ASD and SZ samples; however, by Metz’s (42) standard, the AUC suggests the ADOS-2 algorithm would only be considered a “fair” test for discriminating these two populations, AUC = .73, p < .001. The key aim of this study was to examine the utility of ASD and SZ diagnostic instruments in discriminating these respective disorders. J Autism Dev Disord (2016) 46(1):342–51. J Am Acad Child Adolesc Psychiatry. 1971;118:381-384. 2008;320:539-543. Symptom overlap between ASD and SZ may be most apparent in the negative symptom domain, broadly reflecting deficits in social communication and social–emotional reciprocity. Rather, our clustering provides a “proof of concept” and supports the need for new measures specifically designed and validated to distinguish positive and negative ASD symptoms. These studies would benefit from the inclusion of genetics and characterization of family members to get a clearer sense of the genotype-phenotype associations and predictors of outcome. JM also receives royalties from Guilford Press, Lambert, and Springer. In popular speech, the term "schizophrenic" is often used to describe any kind of disturbed behavior, but in medicine this disorder is defined by fairly precise diagnostic criteria. Rethinking schizophrenia. Sporn AL, Addington AM, Gogtay N, et al. Future research is needed to determine the biological systems that distinguish positive and negative symptom domains across ASD and SZ. For positive symptoms, post hoc comparisons revealed that the ASD group displayed more positive symptoms than both the SZ (p < .001) and TD groups (p < .001), and the SZ group scored marginally higher on this scale than the TD group (p = .051). , – This paper sets out to clarify the position by reviewing the history and current status of the relationship between autism and schizophrenia. Although epidemiological studies of the genetic relationship between autism and schizophrenia are deficient, evidence does exist for shared genetic factors.20 As with the majority of psychiatric disorders and other common conditions, genetic complexity is compounded by phenotypic complexity. We see children with ASD who have emerging psychotic symptoms. Unique features included lower gray matter volume in the amygdala, caudate, and frontal and medial gyrus for schizophrenia, and lower gray matter volume in the putamen for autism. 29. 36. 24. • Children with autism are complex and at high risk for mental health conditions. The boundaries of schizophrenia. 35. This decision was made to ensure ability to accurately self-report during diagnostic assessments. doi: 10.1203/PDR.0b013e318212c196, 27. Dual Diagnosis. Indian J Psychiatry (2010) 52(2):191. doi: 10.4103/0019-5545.64591, 13. SZ features are typically clustered into positive and negative symptom domains (31–33). As the pattern of main effects and post hoc comparisons for all ANCOVAs after controlling for sex and IQ was the same as the original ANOVAs reported above, we do not report these analyses in detail. A recurring issue is the overlap and boundaries between Intellectual Developmental Disorder (IDD), ASD and Schizophrenia Spectrum Disorders (SSD). These results suggest that, when making a differential diagnosis between ASD and SZ, clinicians may benefit from focusing on the presence or absence of positive ASD and SZ symptoms. The phenomenology of childhood psychoses. Schizophrenia and autism are two completely different neuro-psychological disorders. These analyses suggest that the key findings from our analyses were unlikely to be confounded by sex or IQ. As the DSM-5 categorizes disorders primarily on symptom presentation, a key objective of RDoC is to work towards a classification system that clusters disorders based on biologically meaningful mechanisms—with the ultimate goal of better targeting optimal treatments (7). In this example, the first individual displays the absence of a typical behavior (negative symptom), whereas the second displays the presence of an atypical behavior (positive symptom). The purpose of this study was to specify overlapping symptom domains and to identify symptoms that can reliably differentiate adults with ASD (n = 53), SZ (n = 39), and typical development (TD; n = 40). Of particular interest, there was a strong, significant correlation between ADOS-Negative and PANSS-Negative, r = 0.58, p < .001, suggesting overlapping content between the two scales. *Correspondence: Dominic A. Trevisan, email@example.com; James C. McPartland, firstname.lastname@example.org, Front. Volkmar FR, Cohen DJ. Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Few positive ASD symptoms were noted in SZ patients, suggesting that ratings of these symptoms may be most helpful in making a differential diagnosis in this context. Positive symptoms in ASD encompass symptomology related to speech abnormalities such as echolalia or unusual intonation, atypical social behaviors such as exaggerated gesture and facial expressions, inappropriate social overtures, and symptoms related to stereotyped and repetitive behaviors or insistence on sameness such as unusual sensory sensitivities, repetitive hand or body movements, rigid insistence on routinized behavior, or circumscribed interests (34).
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